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一种用于预测软组织肉瘤患者生存情况的新型四基因预后标志物。

A Novel Four-Gene Prognostic Signature for Prediction of Survival in Patients with Soft Tissue Sarcoma.

作者信息

Wu Changwu, Gong Siming, Osterhoff Georg, Schopow Nikolas

机构信息

Institute of Anatomy, University of Leipzig, Liebigstraße 20, 04103 Leipzig, Germany.

Sarcoma Center, Department of Orthopedics, Trauma and Plastic Surgery, University Hospital Leipzig, 04103 Leipzig, Germany.

出版信息

Cancers (Basel). 2021 Nov 21;13(22):5837. doi: 10.3390/cancers13225837.

Abstract

Soft tissue sarcomas (STS), a group of rare malignant tumours with high tissue heterogeneity, still lack effective clinical stratification and prognostic models. Therefore, we conducted this study to establish a reliable prognostic gene signature. Using 189 STS patients' data from The Cancer Genome Atlas database, a four-gene signature including DHRS3, JRK, TARDBP and TTC3 was established. A risk score based on this gene signature was able to divide STS patients into a low-risk and a high-risk group. The latter had significantly worse overall survival (OS) and relapse free survival (RFS), and Cox regression analyses showed that the risk score is an independent prognostic factor. Nomograms containing the four-gene signature have also been established and have been verified through calibration curves. In addition, the predictive ability of this four-gene signature for STS metastasis free survival was verified in an independent cohort (309 STS patients from the Gene Expression Omnibus database). Finally, Gene Set Enrichment Analysis indicated that the four-gene signature may be related to some pathways associated with tumorigenesis, growth, and metastasis. In conclusion, our study establishes a novel four-gene signature and clinically feasible nomograms to predict the OS and RFS. This can help personalized treatment decisions, long-term patient management, and possible future development of targeted therapy.

摘要

软组织肉瘤(STS)是一组具有高度组织异质性的罕见恶性肿瘤,目前仍缺乏有效的临床分层和预后模型。因此,我们开展了本研究以建立一个可靠的预后基因特征。利用来自癌症基因组图谱数据库的189例STS患者的数据,建立了一个包含DHRS3、JRK、TARDBP和TTC3的四基因特征。基于该基因特征的风险评分能够将STS患者分为低风险组和高风险组。高风险组患者的总生存期(OS)和无复发生存期(RFS)显著更差,Cox回归分析表明风险评分是一个独立的预后因素。还建立了包含四基因特征的列线图,并通过校准曲线进行了验证。此外,在一个独立队列(来自基因表达综合数据库的309例STS患者)中验证了该四基因特征对STS无转移生存期的预测能力。最后,基因集富集分析表明该四基因特征可能与一些与肿瘤发生、生长和转移相关的通路有关。总之,我们的研究建立了一种新的四基因特征和临床可行的列线图来预测OS和RFS。这有助于个性化治疗决策、患者长期管理以及未来靶向治疗的可能发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31a4/8616347/b4ec0bb2fc42/cancers-13-05837-g001.jpg

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